The bioequivalence study design recommendations for immediate-release solid oral dosage forms in the international pharmaceutical regulators programme participating regulators and organisations: differences and commonalities.

Bioequivalence (BE) studies are considered the standard for demonstrating that the performance of a generic drug product in the human body is sufficiently similar to that of its comparator product. The objective of this article is to describe the recommendations from participating Bioequivalence Working Group for Generics (BEWGG) members of the International Pharmaceutical Regulators Programme (IPRP) regarding the conduct and acceptance criteria for BE studies of immediate release solid oral dosage forms. A survey was conducted among BEWGG members regarding their BE recommendations and requirements related to study subjects, study design, sample size, single or multiple dose administration, study conditions (fasting or fed), analyte to be measured, selection of product strength, drug content, handling of endogenous substances, BE acceptance criteria, and additional design aspects. All members prefer conducting single dose cross-over designed studies in healthy subjects with a minimum of 12 subjects and utilizing the parent drug data to assess BE. However, differences emerged among the members when the drug's pharmacokinetics and pharmacodynamics become more complex, such that the study design (e.g., fasting versus fed conditions) and BE acceptance criteria (e.g., highly variable drugs, narrow therapeutic index drugs) may be affected. The survey results and discussions were shared with the ICH M13 Expert Working Group (EWG) and played an important role in identifying and analyzing gaps during the harmonization process. The draft ICH M13A guideline developed by the M13 EWG was endorsed by ICH on 20 December 2022, under Step 2.

A 2D chiral microcavity based on apparent circular dichroism.

Engineering asymmetric transmission between left-handed and right-handed circularly polarized light in planar Fabry-Pérot (FP) microcavities would enable a variety of chiral light-matter phenomena, with applications in spintronics, polaritonics, and chiral lasing. Such symmetry breaking, however, generally requires Faraday rotators or nanofabricated polarization-preserving mirrors. We present a simple solution requiring no nanofabrication to induce asymmetric transmission in FP microcavities, preserving low mode volumes by embedding organic thin films exhibiting apparent circular dichroism (ACD); an optical phenomenon based on 2D chirality. Importantly, ACD interactions are opposite for counter-propagating light. Consequently, we demonstrated asymmetric transmission of cavity modes over an order of magnitude larger than that of the isolated thin film. Through circular dichroism spectroscopy, Mueller matrix ellipsometry, and simulation using theoretical scattering matrix methods, we characterize the spatial, spectral, and angular chiroptical responses of this 2D chiral microcavity.

[Excelling in the AI Era: Cultivating AI Literacy].

In light of the rapid advancements in artificial intelligence (AI), the future of the nursing profession is expected to be closely intertwined with AI applications. In response to this challenge, nursing educators must cultivate AI literacy in students to ensure their ability to communicate and collaborate effectively with their interdisciplinary peers. Nursing educators should comprehend the essence of AI literacy, integrate AI literacy into their curriculum designs, and regularly assess the effectiveness of AI literacy cultivation efforts among their students to ensure nursing graduates are able to effectively fulfill their roles in nursing and healthcare. The purpose of this paper is to explain the essence of AI literacy, approaches for cultivating AI literacy in students, and methods for assessing AI literacy with the aim of educating nursing students to become competent nurses for tomorrow.

Development and Validation of a Breastfeeding Health Literacy Scale (BFHLS) for Taiwanese Pregnant Women.

BACKGROUND: Breastfeeding is the best source of nutrition for infants. Health literacy is a critical factor affecting breastfeeding rates. RESEARCH AIMS: The aim of this research was to develop and test the Breastfeeding Health Literacy Scale to determine its validity and reliability. METHODS: This study featured a cross-sectional telephone survey design. Researchers reviewed the literature and used expert opinions to develop the content-validated 30-item Breastfeeding Health Literacy Scale covering five dimensions. We examined internal consistency, exploratory factor analysis, and confirmatory factor analysis to assess reliability and construct validity. A Taiwanese government organization provided potential participants' contact information. After mailing an invitation letter, researchers phoned all participants to invite participation, obtain oral consent and complete a Breastfeeding Health Literacy Scale and collect demographic data. RESULTS: Participants (N = 300) had a mean age of 31.8 (SD = 4.66) years. The item-level content validity index was 0.67 to 1.00 and scale-content validity index was 0.94. After performing exploratory factor analysis, three factors were extracted. Examining content factor analysis for the three factors resulted in χ2/df = 2.05; p < .001; goodness of fit index = 0.90; Comparative Fit Index (CFI) = 0.96; and Root Mean Square Error of Approximation (RMSEA) = 0.06. Cronbach's alphas on the total scale and the subscales ranged from 0.87 to 0.94. Women with multigravida, breastfeeding information from physicians and nurses, and previous breastfeeding experience had better breastfeeding health literacy. CONCLUSIONS: Psychometric analysis demonstrated that the newly developed 20-item Breastfeeding Health Literacy Scale is a valid self-assessment instrument. Improving breastfeeding health literacy during pregnancy could help enable breastfeeding success.

Oral metronomic therapy of pancreatic cancer with gemcitabine and paclitaxel co-loaded in lecithin-based Self-Nanoemulsifying preconcentrate (LBSNEP).

This study aimed to evaluate gemcitabine (GEM)/paclitaxel (PTX) co-loaded into a lecithin-based self-nanoemulsifying preconcentrate (LBSNEP) orally administered in a metronomic therapeutic manner against pancreatic cancer. LBSNEP was developed and evaluated, composed of Caproyl 90, Tween80, lecithin, TPGS, and propyl glycol at a ratio of 20:20:30:5:25, resulting in a droplet diameter of approximately 180 nm. Cell viability studies on MIA PaCa-2 demonstrated a synergetic effect at a proportion of 1:2 between PTX and GEM. Additionally, LBSNEP and baicalein (BAI) were demonstrated to prevent GEM from being deaminated by cytidine deaminase. The combination of GEM, PTX, and BAI in the LBSNEP showed good dissolution in simulated gastric fluid. The pharmacokinetic study conducted on rats showed that co-administration of GEM, PTX, and BAI in the LBSNEP enhanced the respective relative oral bioavailability levels of GEM and PTX by 1.5- and 2-fold, respectively, compared to the solution group. The tumor inhibition study was conducted with metronomic therapy at a low daily dose compared to conventional therapy at a higher dose every 3 days. Results indicated that oral metronomic delivery of GEM/PTX/BAI LBSNEP could inhibit tumor growth during administration phase, and that there were similar tumor volumes compared to traditional chemotherapy at day 28 even if the dose of metronomic chemotherapy was 2.2-fold less than that of the latter. In conclusion, a self-nanoemulsifying drug-delivery system for the oral delivery of GEM, PTX, and BAI in a metronomic manner enhanced the therapeutic effect on pancreatic cancer, providing an alternative option for chemotherapy.

Excessive gestational weight gain and emotional eating are positively associated with postpartum depressive symptoms among taiwanese women.

BACKGROUND: Excessive gestational weight gain and emotional eating may be associated with postpartum depression symptoms. This study was designed to identify how gestational weight gain and eating behaviors are related to postpartum depression (PPD) symptoms among women in Taiwan. METHODS: A cross-sectional study was conducted from March 2022 to October 2022 with 318 postpartum women recruited in Taipei, Taiwan. Gestational weight gain (GWG) for the total pregnancy period was recorded as inadequate, adequate, or excessive, based on the 2009 Institute of Medicine recommendations (IOM), accounting for pre-pregnancy body mass index category. Eating behavior at one month postpartum was measured on a 16-item 5-point Likert scale with three subscales: uncontrolled, restrained, and emotional. Maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale with a cutoff score of 13. RESULTS: The prevalence of postpartum depression symptoms (Edinburgh Postnatal Depression Scale ≥ 13) was 23.9% at one month postpartum. Logistic regression analysis revealed that excessive gestational weight gain and emotional eating were positively associated with postpartum depression symptoms at that time. CONCLUSION: Evidence presented here suggests that emotional eating and excessive GWG are associated with PPD symptoms in a Taiwanese population. In addition, it should be a public health priority to ensure a particular focus on mental health during the postpartum period. Healthcare providers should discourage pregnant women from unhealthy eating habits by targeting appropriate GWG and focusing on demand eating to reduce PPD in the postpartum period.

Feeding self-efficacy and feeding outcome expectancy mediate the association between maternal depressive symptoms and responsive feeding.

Previous research has demonstrated a link between maternal depressive symptoms and infant feeding behavior; however, the underlying mechanisms linking the two remain unclear. This study examined the association between maternal depressive symptoms and responsive feeding, and the potential mediating role of feeding self-efficacy and outcome expectancy. A panel study with 487 women, from pregnancy through postpartum, was conducted. Maternal depressive symptoms at one month postpartum were assessed by the Edinburgh Postnatal Depression Scale. Responsive feeding included feeding on demand and unforced feeding domains. Responsive feeding, feeding self-efficacy, and feeding outcome expectancy were assessed at three months postpartum. Maternal depressive symptoms were associated with less responsive feeding, but the association was fully mediated by feeding self-efficacy and feeding outcome expectancy. Infant feeding problems are associated with depressive symptoms in mothers. Health professionals could work with depressed mothers to enhance infant feeding by targeting feeding self-efficacy and feeding outcome expectancy.

Processed Dietary Patterns during Pregnancy Are Associated with Low Birth Weight at Term among Women of Advanced and Non-Advanced Age.

Inappropriate dietary intake during pregnancy is a key factor in low birth weight (LBW). This study compares LBW between healthy and processed dietary patterns by focusing on women of advanced maternal age. A cross-sectional survey was conducted with 327 postpartum women in Taiwan. The participants were assigned to two groups according to their age (≥35 years, n = 151; and 20−34 years, n = 176). An online questionnaire asked women how often they consumed 27 food items during their pregnancy. The prevalence of LBW was higher in the processed dietary pattern (79.3%) than in the healthy pattern (13.78%, p < 0.001). LBW was positively correlated with advanced maternal age (≥35 ages), low pre-pregnancy weight (BMI less than 18.5 kg/m2), insufficient gestational weight gain (GWG), and processed dietary patterns. Older mothers were 5.8 times more likely to have infants with LBW (odds ratio = 5.8; 95% confidence interval 2.0−16.6). A processed dietary pattern was 9.4 times more likely to result in LBW. Insufficient GWG was significantly positively associated with LBW (OR = 4.0; 95%CI 1.4−11.6). Maternal diet during pregnancy is an important modifiable factor for LBW. Prenatal advice should emphasize optimal nutrition, especially in older and underweight women.

Optically Switched Dual-Wavelength Cavity Ring-Down Spectrometer for High-Precision Isotope Ratio Measurements of Methane δD in the Near Infrared.

We report a spectrometer employing optically switched dual-wavelength cavity ring-down spectroscopy (OSDW-CRDS) for high-precision measurements of methane isotope ratios. A waveguide optical switch rapidly alternated between two wavelengths to detect absorption by two isotopologues using near-infrared CRDS. This approach alleviated common-mode noise that originated primarily from temperature and frequency fluctuations. We demonstrated the measurement of δD in natural abundance methane to a precision of 2.3 ‰, despite the lack of active temperature or frequency stabilization of the cavity. The ability of alternating OSDW-CRDS to improve the isotope precision in the absence of cavity stabilization were measured by comparing the Allan deviation with that obtained when frequency-stabilizing the cavity length. The system can be extended to a wide variety of applications such as isotope analysis of other species, kinetic isotope effects, ortho-para ratio measurements, and isomer abundance measurements. Furthermore, our technique can be extended to multiple isotope analysis or two species involved in kinetics studies through the use of multiport or high-speed optical switches, respectively.

Measuring the α-particle charge radius with muonic helium-4 ions.

The energy levels of hydrogen-like atomic systems can be calculated with great precision. Starting from their quantum mechanical solution, they have been refined over the years to include the electron spin, the relativistic and quantum field effects, and tiny energy shifts related to the complex structure of the nucleus. These energy shifts caused by the nuclear structure are vastly magnified in hydrogen-like systems formed by a negative muon and a nucleus, so spectroscopy of these muonic ions can be used to investigate the nuclear structure with high precision. Here we present the measurement of two 2S-2P transitions in the muonic helium-4 ion that yields a precise determination of the root-mean-square charge radius of the α particle of 1.67824(83) femtometres. This determination from atomic spectroscopy is in excellent agreement with the value from electron scattering1, but a factor of 4.8 more precise, providing a benchmark for few-nucleon theories, lattice quantum chromodynamics and electron scattering. This agreement also constrains several beyond-standard-model theories proposed to explain the proton-radius puzzle2-5, in line with recent determinations of the proton charge radius6-9, and establishes spectroscopy of light muonic atoms and ions as a precise tool for studies of nuclear properties.

Mapping temporal and spatial changes in land use and land surface temperature based on MODIS data.

Climate change and the rapid expansion of the built environment have intensified heat stress worldwide. Due to environmental changes and urbanization, some studies show evidence of spatial and temporal changes in heat stress. The objective of this study is to apply spatial analysis to explore temporal and spatial changes in heat stress and to conduct a comparative analysis of land surface temperature (LST) and land use. The results show a significant expansion of the areas where the LST is over 35 °C or between 30 °C and 35 °C. A comparative analysis between the expansion of areas with high LSTs and changing land use types shows that LSTs were indeed higher in 2014 than the values in 2008 and that LSTs remained relatively high in areas where the LST was over 35 °C or between 30 °C and 35 °C. The temperature variation is not significant between urban and rural areas, indicating that heat stress has been extended toward particular rural areas. The cooling effect provided by open space is not significant, so city planners should exert more effort to mitigate extreme heat stress. As a whole, heat stress does change temporally and spatially, and the results of the comparative analysis could be further referenced in future efforts to improve the ability of areas to adapt to heat stress based on various land use patterns.

Critical Role for the NLRP3 Inflammasome in Mediating IL-1ß Production in Shigella sonnei-Infected Macrophages.

Shigella is one of the leading bacterial causes of diarrhea worldwide, affecting more than 165 million people annually. Among the serotypes of Shigella, Shigella sonnei is physiologically unique and endemic in human immunodeficiency virus-infected men who have sex with men. The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, a protein complex composed of NLRP3, apoptosis-associated speck-like protein, and caspase-1, recognizes, and responds to pathogen infection and diverse sterile host-derived or environmental danger signals to induce IL-1ß and IL-18 production. Although the Shigella flexneri-mediated activation of the NLRP3 inflammasome has been reported, the effect of S. sonnei on NLRP3 inflammasome activation remains unclear. We found that S. sonnei induced IL-1ß production through NLRP3-dependent pathways in lipopolysaccharide-primed macrophages. A mechanistic study revealed that S. sonnei induced IL-1ß production through P2X7 receptor-mediated potassium efflux, reactive oxygen species generation, lysosomal acidification, and mitochondrial damage. In addition, the phagocytosis of viable S. sonnei was important for IL-1ß production. Furthermore, we demonstrated that NLRP3 negatively regulated phagocytosis and the bactericidal activity of macrophages against S. sonnei. These findings provide mechanistic insight into the activation of the NLRP3 inflammasome by S. sonnei in macrophages.

Responsive Feeding, Infant Growth, and Postpartum Depressive Symptoms During 3 Months Postpartum.

Responsive feeding is crucial to the formation of life-long healthy eating behavior. Few studies have examined maternal responsive feeding in early infancy among a Chinese population. This prospective study describes maternal responsive feeding and factors associated with maternal responsive feeding, with emphasis on infant growth and maternal depressive symptoms, during the first 3 months postpartum in Taiwan. From 2015 to 2017, 438 pregnant women were recruited and followed at 1 and 3 months postpartum. Maternal responsive feeding at 3 months was measured on a 10-item 5-point Likert-type scale. Maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale with a cutoff score of 10. Infant growth was categorized into four groups based on weight-for-length Z scores from birth to 3 months: no change, increase but in the normal range, increase to overweight, and decrease to underweight. Multiple regression revealed that postpartum depressive symptoms, primipara, and decreased infant weight-for-length Z score were negatively associated with maternal responsive feeding, while exclusive breastfeeding and maternal age younger than 29 years were positively associated with maternal responsive feeding. Heath professionals should educate mothers on responsive feeding, with emphases on first-time and non-exclusive breastfeeding mothers, as well as those with depressive symptoms, advanced maternal age, and infants who are becoming underweight.

The indicators of human capital for hospital-based nursing workforce in Taiwan.

AIM: To develop a hospital-based nursing human capital model for Taiwan. BACKGROUND: Effective nursing management only becomes possible when nurse managers are able to manage and maintain the right equilibrium among human capital components. METHOD: We developed an analytic hierarchy process (AHP) model with 8 dimensions and 31 indicators based on extensive literature review and experts' perceptual assessment. We used expert and purposive sampling and invited 82 nursing professionals to rate the importance of these dimensions and indicators. The AHP process was performed to identify the weightage and prioritize the dimensions and indicators of the nursing human capital. RESULTS: Our analysis showed that, for nursing human capital, health was the most important factor (weight: 34.8%), followed by employee protection (20.4%), work attitude (13.7%), employee stability (10.8%), general nursing training (6.3%), competencies (5.8%), advanced nursing training (4.3%) and clinical nursing experience (3.9%). CONCLUSION AND IMPLICATION FOR NURSING MANAGEMENT: The model would be most useful for nurse administrators in long-range strategic management. Specifically, the model can be used as a reference to form a rating system to analyse nursing human capital. Health promotion programs and employee protection measures targeting nurses could improve nursing human capital in hospitals.

Sideband amplitude modulation absorption spectroscopy of CH4 at 1170 nm.

We report on the method of the sideband amplitude modulation (SAM) to achieve high-sensitivity spectroscopy with a fiber electro-optic modulator (fiber-EOM). This method increases the signal to noise ratio (SNR) by a factor of forty, comparing with conventional absorption spectroscopy. It is a temporal balanced detection to eliminate the intensity noise of the light source, and capable of preserving an undistorted Doppler profile for further quantitative analysis. Taking advantage of the newly developed fiber-EOM, SAM is applicable for various spectroscopies with a simple experimental setup. We performed SAM on CH43ν3 overtone band at 1170 nm using an external cavity Quantum dot laser. We demonstrated that one of the absorption lines buried in the other ten times stronger nearby lines was clearly extracted. SAM shows great potential on the molecular spectroscopy, where the spectrum is complicated and quantitative analysis is required.

IDH-1 deficiency induces growth defects and metabolic alterations in GSPD-1-deficient Caenorhabditis elegans.

NADPH is a reducing equivalent that maintains redox homeostasis and supports reductive biosynthesis. Lack of major NADPH-producing enzymes predisposes cells to growth retardation and demise. It was hypothesized that double deficiency of the NADPH-generating enzymes, GSPD-1 (Glucose-6-phosphate 1-dehydrogenase), a functional homolog of human glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, and IDH-1 (isocitrate dehydrogenase-1) affect growth and development in the nematode, Caenorhabditis elegans (C. elegans). The idh-1;gspd-1(RNAi) double-deficient C. elegans model displayed shrinkage of body size, growth retardation, slowed locomotion, and impaired molting. Global metabolomic analysis was employed to address whether or not metabolic pathways were altered by severe NADPH insufficiency by the idh-1;gspd-1(RNAi) double-deficiency. The principal component analysis (PCA) points to a distinct metabolomic profile of idh-1;gspd-1(RNAi) double-deficiency. Further metabolomic analysis revealed that NADPH-dependent and glutamate-dependent amino acid biosynthesis were significantly affected. The reduced pool of amino acids may affect protein synthesis, as indicated by the absence of NAS-37 expression during the molting process. In short, double deficiency of GSPD-1 and IDH-1 causes growth retardation and molting defects, which are, in part, attributed to defective protein synthesis, possibly mediated by altered amino acid biosynthesis and metabolism in C. elegans.

Watt-level single-frequency tapered amplifier laser using a narrowband interference filter.

We demonstrate a tunable external cavity tapered amplifier laser (ECTAL) using a narrowband interference filter as the wavelength discriminator. The laser is tunable over a wavelength range from 1006 to 1031 nm with an output power of ∼1 W. The amplified stimulated emission of the laser system is suppressed to better than 32 dB. The laser is applied to study the saturation spectroscopy on the R(39) 57-0 line of iodine molecule, which, to our best knowledge, is the first measurement of this line close to the dissociation limit. The linewidth of the a1 component is ∼2 MHz at the iodine vapor pressure of ∼11 Pa, and the pressure-broadening coefficient is ∼156 kHz/Pa. This laser system is also used for the injection seeding of a 1030 nm disk laser to perform hyperfine spectroscopy of muonic hydrogen. To reach a satisfactory condition for disk laser use, the ECTAL is successfully stabilized to the iodine Doppler-free spectroscopy of the P(26) 43-0 line near 515 nm, with continuous locking over 48 h.

Sub-Doppler resolution near-infrared spectroscopy at 1.28 µm with the noise-immune cavity-enhanced optical heterodyne molecular spectroscopy method.

We report on the sub-Doppler saturation spectroscopy of the nitrous oxide (N2O) overtone transition at 1.28 µm. This measurement is performed by the noise-immune cavity-enhanced optical heterodyne molecular spectroscopy technique based on the quantum-dot (QD) laser. A high intra-cavity power, up to 10 W, reaches the saturation limit of the overtone line using an optical cavity with a high finesse of 1.14(5)×105. At a pressure of several mTorr, the saturation dip is observed with a full width at half-maximum of about 2 MHz and a signal-to-noise ratio of 71. To the best of our knowledge, this is the first saturation spectroscopy of molecular overtone transitions in the 1.3 µm region. The QD laser is then locked to this dispersion signal with a stability of 15 kHz at 1 s integration time. We demonstrate the potential of the N2O as a marker because of its particularly rich spectrum at the vicinity of 1.28-1.30 µm where there are several important forbidden transitions of atomic parity violation measurements and the 1.3 µm O-band of optical communication.

Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly pervasive inherited disease in many parts of the world. The complete lack of G6PD activity in a mouse model causes embryonic lethality. The G6PD-deficient Caenorhabditis elegans model also shows embryonic death as indicated by a severe hatching defect. Although increased oxidative stress has been implicated in both cases as the underlying cause, the exact mechanism has not been clearly delineated. In this study with C. elegans, membrane-associated defects, including enhanced permeability, defective polarity and cytokinesis, were found in G6PD-deficient embryos. The membrane-associated abnormalities were accompanied by impaired eggshell structure as evidenced by a transmission electron microscopic study. Such loss of membrane structural integrity was associated with abnormal lipid composition as lipidomic analysis revealed that lysoglycerophospholipids were significantly increased in G6PD-deficient embryos. Abnormal glycerophospholipid metabolism leading to defective embryonic development could be attributed to the increased activity of calcium-independent phospholipase A2 (iPLA) in G6PD-deficient embryos. This notion is further supported by the fact that the suppression of multiple iPLAs by genetic manipulation partially rescued the embryonic defects in G6PD-deficient embryos. In addition, G6PD deficiency induced disruption of redox balance as manifested by diminished NADPH and elevated lipid peroxidation in embryos. Taken together, disrupted lipid metabolism due to abnormal redox homeostasis is a major factor contributing to abnormal embryonic development in G6PD-deficient C. elegans.